Low Dose Olanzapine to the Prophylaxis of Nausea and Vomiting Induced by Chemotherapy in Children and Adolescents

NCT05346731 | Unknown Phase 3

• 1 other identifier: OZONE-V
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

Brief Summary

Chemotherapy-induced nausea and vomiting continues to be a significant problem in children and adolescents. Standard antiemetic therapy, including a 5-HT3 antagonist, aprepitant, and a corticosteroid, achieves complete control in less than 50% of patients. Studies have shown that the addition of large doses of olanzapine improves control, including in children and adolescents. However, olanzapine has not yet been included in standard recommendations in the pediatric population. Studies in adults indicate that the dose of the drug can be halved without loss of effectiveness and with a decrease in toxicity. This open-label, randomized, phase III trial evaluates the efficacy and safety of adding low-dose olanzapine to standard prevention of nausea and vomiting induced by highly emetogenic chemotherapy in children and adolescents.

Conditions

Chemotherapy-induced Nausea and Vomiting

Outcome Measures

Primary Outcomes (3)

• Complete control of vomiting

  proportion of patients who did not have episodes of vomiting and/or use of additional antiemetic drugs (rescue therapy) during the chemotherapy cycle and within 120 hours after its completion

  up to 21 days

• Patient preference

  Proportion of patients who, after crossover, chose to continue treatment with an experimental regimen including olanzapine

  up to 42 days

• Adverce events

  Percentage of patients with grade 3-4 adverse events according to CTCAE v. 5.0. \[Time frame: day(s) of chemotherapy administration and 120 hours after chemotherapy administration\]

  up to 42 days

Secondary Outcomes (2)

• Complete control of acute vomiting

  up to 21 days

• Complete control of chemotherapy-induced nausea and vomiting (CINV)

  up to 21 days

Study Arms (2)

Control group

ACTIVE COMPARATOR

1. Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg) 2. Weight category \> 40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy.

Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant

Olanzapine

EXPERIMENTAL

1. Weight category 30-40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (80 mg), olanzapine (2.5 mg) 2. Weight category \> 40 kg will receive: dexamethasone (5 mg/m2), ondansetron (0.15 mg/kg), aprepitant (125 mg), olanzapine (2.5 mg for \<55 kg, 5 mg for \>55 kg) Note: aprepitant at a dose of 80 mg/day. applied for another 2 days, regardless of the number of days of chemotherapy.

Drug: Ondansetron; Drug: Dexamethasone; Drug: Aprepitant; Drug: Olanzapine

Interventions

Ondansetron DRUG

Ondnsetron will be administered at a dose of 0.15 mg/kg IV/PO every 8 hours on the day(s) of chemotherapy and 3 days after completion of chemotherapy

Control group; Olanzapine

Dexamethasone DRUG

Dexamethasone will be administered at a dose of 5 mg/m2 intravenously/orally once on the day(s) of chemotherapy and 3 days after completion of chemotherapy;

Control group; Olanzapine

Aprepitant DRUG

Aprepitant will be administered based on body weight: body weight 30-40 kg: days 1-3 - 80 mg orally; body weight \> 40 kg: day 1 - 125 mg orally, days 2, 3 - 80 mg orally

Control group; Olanzapine

Olanzapine DRUG

Olanzapine will be administered at a dose of 0.07 mg/kg orally on the day(s) of chemotherapy and 3 days after completion of chemotherapy (rounded up to the maximum multiple of 2.5 mg, maximum daily dose of 5 mg).

Olanzapine

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age from 5 to 18 years.
• Body weight ≥ 30 kg.
• Confirmed diagnosis of malignancy.
• Planned at least 2 cycles of highly emetogenic chemotherapy according to the Pediatric Ontario Cancer Group (POGO) emetogenicity classification.
• ECOG status \< 3.
• Adequate function of internal organs (bilirubin \< 1.5 upper limit of normal (ULN), ALT and AST \<2.5 ULN, creatinine \< 1.5 ULN).
• Ability to swallow study drug.
• The presence of a written voluntary informed consent of the patient and / or his legal representative.

You may not qualify if:

• Treatment with olanzapine or another antipsychotic drug within the last 30 days.
• Planned use of antibiotics from the group of fluoroquinolones or other drugs that have drug interactions with olanzapine and other drugs used in the study (amifostin, citalopram, CYP1A2 inducers or inhibitors).
• The presence of a convulsive syndrome.
• Hypersensitivity to olanzapine or other drugs used in the study.
• Uncontrolled arterial hypertension or cardiovascular disorders, uncontrolled diabetes mellitus, or other diseases and conditions that, in the opinion of the physician, preclude study therapy.
• Severe CINV of any intensity 24 hours or less before the first dose of chemotherapy.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

Zhukov Nikolay

Moscow, 117997, Russia

RECRUITING

MeSH Terms

Conditions

Vomiting

Interventions

Ondansetron; Dexamethasone; Aprepitant; Olanzapine

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Morpholines; Oxazines; Benzodiazepines; Benzazepines

Central Study Contacts

Nikolay Zhukov, MD,PhD

CONTACT

+79264177766; 1cancerdoctor1@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: April 26, 2022
• Study Start: April 1, 2022
• Primary Completion: March 1, 2024
• Study Completion: August 1, 2024
• Last Updated: July 28, 2022

Record last verified: 2022-07

Locations

RU (1)